Abstral sublingual tablet

Abstral is a rapid‑acting fentanyl sublingual tablet approved for the management of breakthrough cancer pain in opioid‑tolerant adults, offering onset of analgesia within minutes due to its highly lipophilic nature and sublingual absorption . It is available in strengths ranging from 100 μg to 800 μg, with an initial recommended dose of 100 μg and careful individual titration to balance efficacy and safety . Abstral carries serious risks—including life‑threatening respiratory depression, addiction, and abuse—and is only dispensed through a restricted REMS program . Metabolism is primarily via CYP3A4, so coadministration with CYP3A4 inhibitors or inducers can markedly alter fentanyl plasma levels; patients must be monitored closely for sedation and respiratory depression . Common adverse effects include nausea, dizziness, and somnolence; patient counseling on proper sublingual administration, avoidance of eating or drinking until complete dissolution, and safe storage is critical .

Indications and Usage

Abstral (fentanyl) sublingual tablets are indicated only for the management of breakthrough pain in cancer patients aged 18 years and older who are already receiving, and are tolerant to, around‑the‑clock opioid therapy for persistent cancer pain . Opioid tolerance is defined as at least one week of use of ≥ 60 mg oral morphine daily, or ≥ 25 μg/h transdermal fentanyl, or equivalent opioid dosing . Abstral is contraindicated in opioid‑naïve patients and not for acute, postoperative, or headache/migraine pain .

Mechanism of Action

Fentanyl is a potent μ‑opioid receptor agonist that inhibits ascending nociceptive transmission, altering pain perception at supraspinal and spinal levels . Its high lipophilicity facilitates rapid transmucosal absorption, producing analgesia faster than oral or buccal formulations .

Dosage and Administration

Strengths: 100 μg, 200 μg, 300 μg, 400 μg, 600 μg, and 800 μg sublingual tablets .

Initial Dose: Always start at 100 μg in opioid‑tolerant patients, then titrate to effective dose while minimizing side effects .

Frequency: Up to four doses per day, with at least 4 hours between doses .

Administration: Place tablet under tongue; allow to dissolve fully (15–30 minutes); do not chew, swallow, eat, or drink until dissolution is complete . If any tablet remains after 30 minutes, it may be swallowed with water.

Contraindications

Opioid‑naïve patients (risk of fatal respiratory depression) 

Management of acute or postoperative pain, including headache/migraine and dental pain 

Known hypersensitivity to fentanyl or any excipient

Warnings and Precautions

Respiratory Depression: Life‑threatening events may occur even at recommended doses; monitor closely, especially during initiation and dose adjustments .

Addiction, Abuse, Misuse: Contains a Schedule II opioid; risk of diversion, abuse, and addiction necessitates REMS enrollment .

Neonatal Opioid Withdrawal: Prolonged use during pregnancy may lead to neonatal withdrawal syndrome.

Central Nervous System (CNS) Depression: Use caution when coadministered with other CNS depressants; may require dose adjustments .

Pharmacokinetics

Absorption: Rapid sublingual uptake; peak plasma concentrations reached in approximately 30 minutes .

Distribution: Highly lipophilic, with large volume of distribution.

Metabolism: Primarily via hepatic CYP3A4 to inactive metabolites .

Elimination: Excreted mainly in urine as metabolites.

Side Effects

Common (≥ 10%):

Nausea and vomiting 

Somnolence, dizziness 

Headache, fatigue

Serious:

Respiratory depression 

Hypotension, bradycardia

Serotonin syndrome (if coadministered with serotonergic drugs)

Drug Interactions

CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin) can increase fentanyl levels, risking fatal respiratory depression; monitor and adjust dose .

CYP3A4 Inducers (e.g., carbamazepine, phenytoin) can decrease fentanyl efficacy and precipitate withdrawal; use with caution .

Other CNS Depressants (e.g., benzodiazepines, alcohol) potentiate sedation and respiratory depression; consider dose reduction and enhanced monitoring .

Patient Counseling

Instruct patients to place the tablet under the tongue and allow complete dissolution without chewing, swallowing, eating, or drinking until dissolved .

Warn about risks of respiratory depression and drowsiness—advise against driving or operating machinery until effects are known.

Emphasize safe storage and disposal to prevent accidental ingestion, particularly by children; keep in original packaging and out of reach .

Enroll patients in 

the Abstral REMS program to ensure understanding of safe use, risks, and proper handling.